Common Endocrine Problems Seen in Primary Care (Part 2) Lecture #34 Jonathan R. Anolik, MD, FACP, FACE Lewis Katz School of Medicine at Temple University
None Conflict of Interest
Topics to be Covered Adrenal Incidentaloma Pituitary incidentaloma and hypopituitarism Male hypogonadism Osteoporosis
Adrenal Incidentaloma Generally, do not evaluate any adenoma < 1 cm unless there is an obvious hormonal syndrome associated with it (hyperaldosteronism (Conn s syndrome), pheochromocytoma, or Cushing s syndrome). Radiologic evaluation should distinguish benign from tumors of concern several options All tumors 1 cm or larger should have hormonal evaluation Consider removal of tumors over 4-6 cm even if benign characteristics unless myelolipoma.
Radiologic Evaluation Non-contrast CT benign if Hounsfield unit measurement is 10 Contrast enhanced CT benign if rapid washout of contrast by 10-15 minutes. Relative washout > 40% and absolute washout > 60% suggests benign MRI compares in phase to out of phase imaging to distinguish benign from concerning lesions FDG-PET can also differentiate benign lesions from those of concern
Normal Adrenals on CT
Adrenal Adenoma on CT
Radiologic Evaluation Lesion found incidentally on an initial study Repeat as adrenal protocol CT or MRI depends a bit on your institution. If benign appearing, repeat non-contrast CT for size after 6-12 months to be sure not growing. If of concern and not having surgery, repeat study in 3-12 months. Some recommend one more study one year later for benign appearing lesions but others do not DO NOT DO BIOPSY UNLESS PHEOCHROMOCYTOMA RULED OUT BIOPSY ONLY HELPFUL IN DIAGNOSING METASTATIC DISEASE BENIGN AND MALIGNANT ADRENAL LESIONS CANNOT BE RELIABLY DISTINGUISHED ON BIOPSY.
Radiologic Evaluation Consider surgery for nodules > 4-6 cm unless consistent with myelolipoma li (Hounsfield < -20). Consider surgery for high density lesions smaller than 4 cm once pheochromocytoma excluded. PET can be helpful here at times.
Hormonal Evaluation of all Incidentally Found Adrenal Nodules 1 cm 1 mg overnight dexamethasone suppression test Normal < 1.8 mcg/dl Cortisol excess > 5 mcg/dl DHEA-S can help usually low if cortisol secreting adrenal adenoma ACTH can help usually low normal or low-normal if cortisol secreting adrenal adenoma Aldosterone/renin ratio If > 20, confirm with another test. Beta blockers can cause falsely elevated ratio by suppressing renin (if spontaneous hypokalemia, undetectable t renin, aldosterone > 20 ng/dl can go right to sampling). Plasma free metanephrine vs 24 hour urine catecholamines Pheochromocytoma is frequently high density on CT
Hormonal Evaluation of all Incidentally Found Adrenal Nodules 1 cm Assuming benign imaging characteristics and initial benign hormonal evaluation, repeat dexamethasone suppression test t after 1-2 years different organizations have given different recommendations on this. Certainly if suppression > 1.8, repeat and also obtain other measurement of cortisol excess 24 hour urine free cortisol or midnight salivary cortisol. Consider endocrine consultation.
From: Approach to the Patient with an Adrenal Incidentaloma. 2010;95(9):4106-4113. doi:10.1210/jc.2010-0457 Figure Legend: Suggested evaluation of an incidentally found adrenal mass. *, Surgery for large masses without a cause that requires resection, e.g. tuberculosis. LN, Late-night; Aldo, aldosterone; Dex, dexamethasone; F/U, follow-up; eval, evaluation; mo, months. Date of download: 2/19/2017 Copyright 2010 by The Endocrine Society
Pituitary Incidentaloma Hypopituitarism Pituitary incidentaloma all should undergo hormonal evaluation and if initial study a brain MRI or CT, get dedicated pituitary MRI with and without contrast. Repeat MRI scan of the pituitary 6 months after the initial scan if the incidentaloma is a macro-incidentaloma ( 1 cm) and 1 year after the initial scan if it is a microincidentaloma (< 1 cm). In patients whose incidentaloma does not change in size, suggest repeating the MRI every year for macro and every 1 2 yr in micro for the following 3 yr, and gradually less frequently thereafter Visual fields if near chiasm
MRI Pituitary
MRI Pituitary Adenoma
Pituitary Incidentaloma Indications for Surgery A Visual Field deficit due to the lesion. Other visual abnormalities, such as ophthalmoplegia or neurological compromise due to nerve compression by the lesion. Lesion abutting or compressing the optic nerves or chiasm on MRI. Pituitary apoplexy with visual disturbance. Hypersecreting tumors other than prolactinomas
Pituitary Incidentaloma Screen for Hormonal Excess Prolactin ideally get with dilution to avoid issues with hook effect (falsely low measurement due to overwhelming of antibodies by very high prolactin). Growth hormone screen with IGF-1 Thyroid hormone screen with TSH and Free T4 Cortisol late night salivary cortisol x 2 or 24 hour urine free cortisol +/- ACTH Most non-functional adenomas are gonadotroph adenoma but non-secretory
Pituitary Incidentaloma Screen for Hypopituitarism Most important in macro-incidentaloma Adrenal AM cortisol (ACTH not helpful) < 3 indicative of adrenal insufficiency > 15 normal 3-15 do ACTH stimulation test Thyroid Free T4 (TSH not helpful and can confuse) Gonadal (be sure prolactin not elevated) Men - LH, FSH testosterone t t (early AM) +/- SHBG Women LH, FSH, Estradiol Growth hormone Can do IGF-1 as screen or if concern do GH stimulation testing random GH not helpful
Pituitary Incidentaloma Screen for Hypopituitarism No need to repeat testing in micro-incidentaloma If macro, repeat testing at 6 months and then yearly or use growth on scanning as indication usually no progression to hypopituitarism if lesion not growing
From: Pituitary Incidentaloma: An Endocrine Society Clinical Practice Guideline. 2016;96(4):894-904. doi:10.1210/jc.2010-1048 [Modified from Molitch ME: J Clin Endocrinol Metab 80:3 6, 1995 (49).] Date of download: 2/19/2017 Copyright 2011 by The Endocrine SocietyThis article is published under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License (CC-BY-NC-ND; http://creativecommons.org/licenses/by-nc-nd/4.0/).
Male Hypogonadism More specific signs and symptoms Incomplete or delayed sexual development, eunuchoidism Reduced sexual desire (libido) and activity Decreased spontaneous (early AM) erections Breast discomfort, gynecomastia Loss of body (axillary and pubic) hair, reduced shaving Very small (especially <5 ml) or shrinking testes Inability to father children, low or zero sperm count Height loss, low trauma fracture, low bone mineral density Hot flushes, sweats
Male Hypogonadism Less specific signs and symptoms Decreased energy, motivation, initiative, and self-confidence Feeling sad or blue, depressed d mood, dysthymia Poor concentration and memory Sleep disturbance, increased sleepiness Mild anemia (normochromic, normocytic, in the female range) Reduced muscle bulk and strength Increased body fat, body mass index Diminished physical or work performance
Male Hypogonadism Measure testosterone before 10 AM Never treat based on a single measurement Consider measuring SHBG unless you know your lab does accurate testing for free or bioavailable il bl testosterone Evaluation of androgen deficiency should not be done during an acute or subacute illness.
Male Hypogonadism If testosterone low, repeat with prolactin, LH and FSH If primary hypogonadism and no obvious cause, get genetic testing for Klinefelter s DEXA scan in men with marked hypogonadism If secondary, get MRI if testosterone level < 150 ng/dl or if there is suggestion of hypopituitarism, mass effect, hyperprolactinemia, visual field defect. Screen iron studies and at least one other pituitary hormone level (e.g. Free T4 and TSH)
Potential Benefits of Androgen Therapy
Monitoring of therapy Male Hypogonadism Hematocrit stop it 54% until level comes down DEXA 2 years after initiating therapy (use T score age > 50, Z score if younger Age > 40, repeat prostate exam and PSA at 3-6 month follow up visit Get urology evaluation if PSA rises by 1.4 ng/ml in a one year period, gy y g y p abnormal prostate exam or bladder outlet symptoms
Hematocrit > 50 Male Hypogonadism Contraindications to Therapy Untreated severe obstructive sleep apnea Severe lower urinary tract symptoms Uncontrolled or poorly controlled heart failure Those desiring fertility Prostate cancer, nodule or induration PSA 4 or 3 if high risk of prostate cancer
Male Hypogonadism Topical preferred therapy gel vs patch Can use injectable but may have higher h risks due to peaks and valleys. Re-evaluate evaluate after 3-6 months and then every 6-12 months (Testosterone is controlled so should check state database and new prescription needed every 6 months) Aim for mid normal range for age If using IM, aim for level of 400-700 ng/dl one week after injection
Male Hypogonadism Journal of Clinical Endocrinology & Metabolism, June 2010, Vol. 95(6):2536 2559
Side effects of testosterone therapy Lowering of sperm count Gynecomastia Possible increased risk of prostate cancer (or growth of undiagnosed cancers) Increase in prostate size with hbladder outlet symptoms Polycythemia Worsening of CHF Worsening of obstructive sleep apnea Phlebitis Possible increased cardiovascular risk, especially in high h risk individuals id
Male Hypogonadism Do not treat all older men with low testosterone evaluate on case by case basis Alternatives to testosterone therapy not as well studied Clomiphene citrate t most common dose 25 mg daily benefits are it is a pill, not controlled, and does not lower sperm count HCG therapy helpful if previous testosterone therapy with desire for fertility can take 18 months or more for spermatogenesis to return spontaneously. Aromatase inhibitors (anastrozoleand letrozole) l least well studied d
Male Hypogonadism World J Nephrol. 2015 May 6; 4(2): 245 253.
Post-Menopausal Osteoporosis Who to screen with DEXA? Age 65 History of fragility fracture Starting or taking glucocorticoids long-term ( 3 months) Radiologic osteopenia Clinical risk factors low body weight, smoker, family history of spine or hip fracture esp at younger age, early menopause, secondary osteoporosis, excessive alcohol When to do vertebral fracture assessment (VFA) Concern that treatment needed but FRAX under recommended threshold
DEXA
Post-Menopausal Osteoporosis When and how to screen for secondary osteoporosis When if Z score -2 or lower or signs/symptoms of other disease How celiac disease (e.g.ttg), Vitamin i D level, l PTH level, l SPEP, TSH, 24 hour urine calcium/creat
Who to treat? Post-Menopausal Osteoporosis FRAX > 3% risk of hip fracture or > 20% risk of major osteoporotic fracture in next 10 years Fragility fracture either clinical or radiologic (VFA vertebral fracture assessment) To be on long term (> 3 month) steroids and T score < -1.0 To be on anastrazole therapy for breast cancer and T score < -1.0
How to treat Post-Menopausal Osteoporosis Limit i alcohol, l smoke cessation, encourage exercise, try to prevent falls Vitamin D 800-2000 units daily (max 4000 units) Ensure sufficient calcium intake 1000-1200 1200 mg by diet and/or supplement Bisphosphonate esp alendronate, risedronate, or zoledronic acid Denosumab Teriparatide/abaloparatide Raloxiphene
How long to treat Post-Menopausal Osteoporosis If mild to moderate osteoporosis, treat t for 3 years with IV bisphosphonate or 5 years with oral and then can stop and evaluate over time via DEXA If severe, keep on therapy +/- drug holiday Teriparatide/abaloparatide treat for 18 months to 2 years and then switch to antiresorptive only therapy that is anabolic Denosumab need to keep on long term possible rebound loss when stopped Raloxifene no documented benefit on hip
Questions?